Jiří Masopust

Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study.

BackgroundAntipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication.MethodsWe investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index.ResultsD-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers.ConclusionsThe results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Assessment of risk of venous thromboembolism and its possible prevention in psychiatric patients.

Aims:  The aim of the present study was to compile a specific algorithm of prevention of venous thromboembolism in hospitalized psychiatric patients because this specific issue has not been addressed sufficiently in the literature.

Visual mismatch negativity among patients with schizophrenia

Event related potentials (ERPs) provide an insight into sensory and cognitive processes in health and disease. Studies of an ERP negative amplitude deflection elicited by a change in a series of auditory stimuli is known as mismatch negativity (MMN). The generation of MMN is impaired in schizophrenia. Its deficit is associated with lower everyday functioning and may be also interpreted as the marker of progression in schizophrenia. MMN elicited by visual stimuli (vMMN) was described by several research teams, but it has not been investigated in schizophrenia as yet. Using a motion-direction paradigm, we elicited visual MMN in 24 patients with schizophrenia and schizoaffective disorder. The vMMN was computed as differences in areas under curve of visual ERPs to standard and deviant motion-direction stimuli recorded from midline derivations at the interval of 100-200 ms. They were compared between groups of patients with schizophrenia and healthy controls. The significantly smaller vMMN indicated an impaired generation of mismatch negativity in patients with schizophrenia. In secondary analyses there was an association of vMMN impairment among patients with higher dose of medication, lower level of functioning and the presence of deficit syndrome. This impairment appears analogous to the impairment of MMN in the auditory domain and is probably related to early visual information processing. Its relationship to cognitive functioning of patients with schizophrenia deserves further attention.

Risk of venous thromboembolism during treatment with antipsychotic agents

The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first‐generation low‐potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second‐generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE.

Anti-NMDA receptor antibodies in patients with a first episode of schizophrenia

Background Encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDA-R) is classified as an autoimmune disorder with psychotic symptoms, which are frequently dominant. However, it remains unclear how frequently NMDA-R antibodies lead to a condition that mimics psychosis and first-episode schizophrenia. In our work, we investigated the presence of antibodies against NMDA-R in patients with first-episode psychosis (FEP) in comparison with healthy volunteers. Methods This study included 50 antipsychotic-naïve patients with FEP (including 21 women) and 50 healthy volunteers (including 21 women). The mean age of the patients was 27.4 (±7.4) years and that of the healthy controls was 27.0 (±7.3) years. Antibodies against NMDA-R in the serum were detected by immunofluorescence. Results None of the investigated patients with an FEP and none of the healthy controls showed positive antibodies against NMDA-Rs. Conclusion According to results of studies, a small proportion of patients with an FEP possess antibodies against NMDA-R. However, the extent to which this finding contributes to the etiopathogenesis of the response to antipsychotic medication and whether immunomodulatory therapy is indicated in these cases remains uncertain.

Antipsychotic drugs as a risk factor for venous thromboembolism

Objective. We assessed whether antipsychotic drugs represent a risk factor for venous thromboembolism by comparing the prevalence of antipsychotic drugs use in a population of patients with venous thromboembolism versus a group of individuals treated for hypertension. Methods. We identified 266 patients (141 women) diagnosed as having venous thromboembolism at the average age of 43.1±11 years who had been hospitalized in the University Hospital in Hradec Králové from 1 January 1996 to 31 December 2004. Two hundred and seventy-four patients (140 women) with arterial hypertension, with an average age of 48.3±8.8 years, represented the control population. Results. Use of antipsychotic drugs was moderately more frequent in the group of patients with venous thromboembolism as compared with the control group subjects (4.89 vs. 1.82%; odds ratio 2.76; 95% confidence interval=1.01–7.55). Discussion. We discuss the possible mechanisms of venous thromboembolism induced by antipsychotic agents – hypoactivity, blood status, obesity, abnormal coagulation, autoimmune mechanisms, and hyperhomocysteinemia. Conclusion. Our results indicate the possibility of an increased risk for venous thromboembolism in patients using antipsychotic drugs. It is necessary to seriously consider this possible adverse effect owing to its potentially fatal consequences.

Common yew intoxication: a case report

IntroductionTaxine alkaloids cause fatal poisoning, in particular due to the compound’s toxic effect on the cardiovascular apparatus.Case presentationWe describe the case of a 39-year-old Caucasian man with common yew intoxication for whom cardiopulmonary resuscitation using all available methods, although delayed and extended, was successful.ConclusionsExtended and delayed cardiopulmonary resuscitation can be used successfully to treat common yew intoxication.

Treatment of behavioral and psychological symptoms of dementias with psychopharmaceuticals: a review

Behavioral and psychological symptoms represent common complications in patients with different types of dementia. Predominantly, they comprise psychosis, agitation and mood disorders, disinhibited behavior, impairment of the sleep and wakefulness rhythm, wandering, perseveration, pathological collecting, or shouting. Their appearance is related to more rapid progression of the disease, earlier institutionalization, use of physical restraints, and higher risk of mortality. Consequently, appearance of behavioral and psychological symptoms of dementia leads to higher costs of care provided and greater distress for caregivers. Clinical guidelines recommend nonpharmacological approaches as the first choice in the treatment of behavioral and psychological symptoms. Pharmacological therapy should be initiated only if the symptoms were not the result of somatic causes, did not respond to nonpharmacological interventions, or were not caused by the prior medication. Acetylcholinesterase inhibitors, memantine, antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines are used. This review summarizes the current findings about the efficacy and safety of the treatment of the neuropsychiatric symptoms in dementias with psychopharmaceuticals. Recommendations for treatment with antipsychotics for this indication are described in detail as this drug group is prescribed most often and, at the same time, is related to the highest risk of adverse effects and increased mortality.

P03-244 - Cardiometabolic risk in patients with schizophrenia

Introduction Patients with schizophrenia have at least 20 years shorter life spam compared with general population that is primarily caused by their cardiovascular morbidity. Aims The aim of this cross-sectional study was to assess the prevalence of cardiometabolic risk factors in a sample of Czech patients with schizophrenia and related diseases and to predict a risk of premature cardiovascular mortality in this population. Methods We reviewed data from 129 outpatients treated in specialized outpatient clinic for psychoses. The main collected variables included basic physical parameters (height, weight, waist circumference, blood pressure), smoking habits, laboratory data (glucose level, serum lipids levels) and ECG. Finally, we compared the studied group with a matched sample from general population in Czech Republic regarding the cardiovascular risk factors. Results Our results show that the most prevalent risk factors are overweight (70% of patients have BMI over 25), dyslipidaemia (70% of patients) and smoking (43% of patients). According to SCORE diagram, there is a high risk of fatal cardiovascular event in ten years in 10% of the study group. The percentage gets even higher (up to 24%) when the latest European guidelines for cardiovascular disease prevention were used to calculate the risk. Conclusions Our outcomes indicate even higher cardiometabolic morbidity in patients with psychoses than referred in literature.

P03-62 - Markers of thrombogenesis are activated in not-yet treated acute schizophrenia

Objectives Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism (VTE) in schizophrenia. The aim of the study was to ascertain whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication. Methods We investigated plasma levels of markers indicating activation of coagulation (D-dimers) and platelets (solubile P-selectin, sP-selectin) in a group of nine men and nine women with acute schizophrenia who had not yet been treated with antipsychotics (age 29.8±9.1 years; body mass index 23.3±5.1), and eighteen healthy volunteers matched for age, gender and body mass index. Results D-dimers (median 0.38 vs 0.22 mg/l; P=0.049) as well as sP-selectin (median 195.9 vs 111.9 ng/ml; P=0.008) plasma levels were significantly increased in the group of patients with acute schizophrenia as compared to healthy volunteers. Conclusions The results suggest that at least a part of venous thromboembolic events in patients with schizophrenia may rather be induced by pathogenetic mechanisms related to psychosis than caused by antipsychotic treatment. Finding an exact cause of VTE in schizophrenia is necessary for its efficient treatment and prevention. We are aware of the pilot character of our data, and continue to involve more patients and healthy volunteers into the research.